The aim of the research is to discover the underlying reactions responsible for the carcinogenicity of nitroso compounds and to ascertain whether there are protective mechanisms by which the cell can minimize the damage produced by these agents. The hypothesis that carcinogenesis is due to the formation and persistence in DNA of the promutagenic base, 06-methylguanine, is being studied. The reactions responsible for the formation of, and subsequent loss of this product are being studied in a number of different tissues known to differ in their susceptibility to the carcinogenic insult produced by the nitrosamines. At present, all of the data collected is consistent with the hypothesis and it appears that the relative resistence of the liver to carcinogenesis is due to the high efficiency with which this abnormal purine can be removed from liver DNA. BIBLIOGRAPHIC REFERENCES: Pegg, A.E. (1976) Alkylation of liver DNA by dimethylnitrosamine: Effect of dose on 06-methylguanine levels. J. Natl. Cancer Inst., in press. Pegg, A.E. (1976) Formation and metabolism of alkylated nucleosides: Possible role in carcinogenesis by nitroso compounds and alkylating agents. Adv. Cancer Res., in press.